The following are brief descriptions of three studies that are being pursued: 1) The observation has been made that the isolated tracheal smooth muscle preparation from the rat, when exposed to high concentrations of isoproterenol at frequent intervals, will eventually lose much of its sensitivity to the relaxing action of this beta agonist. An investigation is currently underway to elucidate the molecular mechanism that is responsible for the observed loss of sensitivity to isoproterenol in the isolated rat tracheal muscle. 2) An effort is currently being made to develop an autoradiographic technique and procedure that eventually will disclose the manner in which various spasmolytic agents modify the extent of accumulation of calcium at various intracellular loci in vascular and other types of smooth muscle fibers. 3) The effects of various concentrations of mobilizable calcium on the configuration and position of dose-repsonse curves generated by excitatory drugs in various smooth muscle preparations are currently being determined. Once this work is completed, we will investigate the types of changes that a number of different spasmolytic agents induce in the configuration and position of this series of dose-response curves. These data will be anlyzed in a manner that, hopefully, will help pinpoint the modes and loci of action of the spasmolytic agents in smooth muscle fibers.